Frontiers in Neuroscience
·
2021
·
IF 4.677
Wang Rui,Hong Ming,Huang Jingyi,Zhou Na,Zhang Yao,Xu Siyuan,Liu Jiaye,Yuan Junjie,Zhang Lusiqi,Huang Linyuan,Huang Ping,Tan Bo,Cao Hong-ying
Aim: This research aimed to investigate the neurotoxicity of low-dose cyclophosphamide (CYP) on the urinary bladder of rats by in vivo and in vitro studies.Methods: To establish CYP-induced cystitis rat model, rats were treated with three intraperitoneal injections of CYP (25 mg/kg) in a week. During treatment, the up-down method was used to assess the mechanical withdrawal threshold. On day 8, urodynamic test and bladder smooth muscle contractility study, including the contraction of bladder strips to electrical field stimulation (EFS, 2–64 Hz), carbachol (CCh, 10–8–10–5 M) and KCl (120 mM), were performed to evaluate the function of bladder function. Body weight and bladder weight were also recorded. Morphometric analysis using an optical microscope and transmission electron microscope was performed to observe the changes of microstructure and submicrostructure of the bladder. The major pelvic neurons were isolated and treated with acrolein (the main CYP metabolite) to assess apoptosis in vitro. RT-PCR assays were used to quantify the mRNA expression levels of Nlrp6, Asc, Casp11 and Casp1 in bladder tissues and primary neurons.Results: After CYP injections, the body weights decreased, but the bladder weights increased in the model group. The mechanical withdrawal threshold of the cystitis model remained at a low level. The morphometric analysis suggested bladder inflammation and neuroinflammation in the bladder of the cystitis rat model. Urodynamic test revealed that, the amplitude, the pressure baseline, the peak pressure and pressure threshold of model rats significantly increased after CYP treatment. The muscle strips of model rats exhibited significantly higher contractility caused by EFS and CCh than the controls. Apoptotic cells appeared at the highest concentration group (100 μM acrolein) after 6 h of acrolein incubation in apoptosis assay of primary neurons. The mRNA expression levels of Nlrp6 and Casp11 were significantly increased in the cystitis rat model and in the acrolein-treated neurons.Conclusions: Low-dose CYP treatment was confirmed to induce nerve injury, which leading to bladder pain and overactive bladder in female rats, and the up-regulation of Nlrp6 and Casp11 may contribute to these pathological changes.
研究领域:
药理学
·
神经科学
·
泌尿学
✓ 已验证
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Tianmin Tang,Shuying Kong,Junyi Xie,Qiurong Deng,Cong Lai,Shuanshuan Guo,Hao Yu,Jianhua Zhou
Intravesical Bacillus Calmette–Guérin (BCG) immunotherapy is a standard treatment for intermediate-risk and high-risk nonmuscle-invasive bladder cancer. The prolonged duration of BCG in the bladder can enhance the immunotherapeutic efficacy. However, intravesical BCG is rapidly excreted with urine by urination at 2 h postinstillation, compromising therapeutic outcomes. Here, this study develops a floating drug delivery system based on air microbubbles to achieve long-term retention of BCG in the bladder. By encapsulating BCG within floating air microbubbles, we successfully develop BCG-loaded microbubbles (BCG-MBs) that are capable of prolonged release of BCG in the bladder. Compared with conventional intravesical BCG immunotherapy, intravesical instillation of BCG-MBs induces more durable immune responses and demonstrates enhanced therapeutic efficacy in SD rats with orthotopic bladder cancer. Furthermore, the floating drug delivery system based on air-microbubbles not only represents a potential intravesical drug carrier for bladder cancer, but also a versatile platform that can encapsulate diverse therapeutic agents, thereby showing great potential applications in immunotherapy, targeted drug delivery, and combination therapy.
研究领域:
免疫治疗
·
药物递送
·
泌尿学
·
癌症研究
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2021
·
IF 11.614
Huiling Chen,Kaiqiang Hu,Yaru Liang,Yuqi Gao,Chenye Zeng,Kang Xu,Xiaojin Shi,Liyuan Li,Yuemiao Yin,Yi Qiao,Ying Qiu,Qingfei Liu,Zhao Wang
Although primary vesical calculi is an ancient disease, the mechanism of calculi formation remains unclear. In this study, we established a novel primary vesical calculi model with d , l -choline tartrate in mice. Compared with commonly used melamine and ethylene glycol models, our model was the only approach that induced vesical calculi without causing kidney injury. Previous studies suggest that proteins in the daily diet are the main contributors to the prevention of vesical calculi, yet the effect of fat is overlooked. To assay the relationship of dietary fat with the formation of primary vesical calculi, d , l -choline tartrate-treated mice were fed a high-fat, low-fat, or normal-fat diet. Genetic changes in the mouse bladder were detected with transcriptome analysis. A high-fat diet remarkably reduced the morbidity of primary vesical calculi. Higher fatty acid levels in serum and urine were observed in the high-fat diet group, and more intact epithelia in bladder were observed in the same group compared with the normal- and low-fat diet groups, suggesting the protective effect of fatty acids on bladder epithelia to maintain its normal histological structure. Transcriptome analysis revealed that the macrophage differentiation-related gene C–X–C motif chemokine ligand 14 ( Cxcl14 ) was upregulated in the bladders of high-fat diet-fed mice compared with those of normal- or low-fat diet-fed mice, which was consistent with histological observations. The expression of CXCL14 significantly increased in the bladder in the high-fat diet group. CXCL14 enhanced the recruitment of macrophages to the crystal nucleus and induced the transformation of M2 macrophages, which led to phagocytosis of budding crystals and prevented accumulation of calculi. In human bladder epithelia (HCV-29) cells, high fatty acid supplementation significantly increased the expression of CXCL14. Dietary fat is essential for the maintenance of physiological functions of the bladder and for the prevention of primary vesical calculi, which provides new ideas for the reduction of morbidity of primary vesical calculi.
研究领域:
泌尿学
·
营养学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
·
2024
·Vol. 43
·期 1
·1-19
·
IF 11.4
Liang Mingkang,Wang Yongqiang,Liu Lisha,Deng Dashi,Yan Zeqin,Feng Lida,Kong Chenfan,Li Chenchen,Li Yuqing,Li Guangzhi
Background CRISPR-Cas13a is renowned for its precise and potent RNA editing capabilities in cancer therapy. While various material systems have demonstrated efficacy in supporting CRISPR-Cas13a to execute cellular functions in vitro efficiently and specifically, the development of CRISPR-Cas13a-based therapeutic agents for intravesical instillation in bladder cancer (BCa) remains unexplored.
Methods In this study, we introduce a CRISPR-Cas13a nanoplatform, which effectively inhibits PDL1 expression following intravesical instillation. This system utilizes a fusion protein CAST, created through the genetic fusion of CRISPR-Cas13 and the transmembrane peptide TAT. CAST acts as a potent transmembrane RNA editor and is assembled with the transepithelial delivery carrier fluorinated chitosan (FCS). Upon intravesical administration into the bladder, the CAST-crRNAa/FCS nanoparticles (NPs) exhibit remarkable transepithelial capabilities, significantly suppressing PDL1 expression in tumor tissues.To augment immune activation within the tumor microenvironment, we integrated a fenbendazole (FBZ) intravesical system (FBZ@BSA/FCS NPs). This system is formulated through BSA encapsulation followed by FCS coating, positioning FBZ as a powerful chemo-immunological agent. Results In an orthotropic BCa model, the FBZ@BSA/FCS NPs demonstrated pronounced tumor cell apoptosis, synergistically reduced PDL1 expression, and restructured the immune microenvironment. This culminated in an enhanced synergistic intravesical instillation approach for BCa. Consequently, our study unveils a novel RNA editor nanoagent formulation and proposes a potential synergistic therapeutic strategy. This approach significantly bolsters therapeutic efficacy, holding promise for the clinical translation of CRISPR-Cas13-based cancer perfusion treatments.
研究领域:
癌症治疗
·
分子生物学
·
纳米技术
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2023
·Vol. 11
·期 14
·4948-4959
·
IF 6.6
Lulu Wang,Fan Qi,Luopeng Bi,Jiao Yan,Xiaoqing Han,Yanjing Wang,Panpan Song,Yanbo Wang,Haiyuan Zhang
Bladder cancer (BC), such as non-muscle invasive bladder cancer (NMIBC), has a significantly high recurrence rate even after intravesical therapy because traditional intravesical chemotherapeutic drugs have short retention time in the bladder and lack efficient uptake in BC cells. Pollen structure usually shows potent adhesion ability to tissue surfaces, different from traditional electronic interaction or covalent binding. 4-Carboxyphenylboric acid (CPBA) has high affinity to sialic acid residues that are overexpressed on BC cells. In the present study, hollow pollen silica (HPS) nanoparticles (NPs) were prepared and modified with CPBA to form CHPS NPs, which could be further loaded with pirarubicin (THP) to form THP@CHPS NPs. THP@CHPS NPs showed high adhesion to skin tissues and could be more efficiently internalized by a mouse bladder cancer cell line (MB49) than THP, inducing more significant apoptotic cells. After intravesical instillation into a BC mouse model through an indwelling catheter, THP@CHPS NPs could more significantly accumulate at the bladder than THP at 24 h post-instillation, and after 8 days of intravesical treatments, magnetic resonance imaging (MRI) revealed that the bladders treated with THP@CHPS NPs showed more smooth bladder lining and more reduction in size and weights than those with THP. Moreover, THP@CHPS NPs exhibited excellent biocompatibility. THP@CHPS NPs hold great potential for intravesical treatment of bladder cancer.
研究领域:
肿瘤学
·
纳米技术
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Composites and Hybrid Materials
·
2024
·Vol. 8
·期 1
·1-19
·
IF 23.2
Ye Fangdie,Ye Chen,Zhao Yufeng,Li Weijian,Zhang Jinhao,Ou Yuxi,Chen Ziang,Cheng Zhang,Zhang Jing,Ali Shujaat,Qureshi Omer Salman,Liu Yufei,Dai Xiangpeng,Huang Hang,Jiang Haowen
Bladder cancer (BLCA), particularly due to the high recurrence and progression rates of non-muscle-invasive bladder cancer (NMIBC), is a significant global health challenge. Current treatments, such as Bacillus Calmette-Guérin (BCG) immunotherapy and intravesical chemotherapy, often cause substantial side effects and exhibit limited efficacy, highlighting the urgent need for novel therapeutic strategies. Single-cell spatial transcriptomic advancements have identified cuproptosis as a critical pathway in BLCA, presenting a promising target for treatment. In this study, these insights were leveraged to design Cu-VT nanoparticles (NPs), an innovative composite material that combines the unique properties of copper ions and the natural flavonoid vitexin, to induce cuproptosis. Cu-VT NPs could effectively induce apoptosis and oxidative stress in BLCA cells concurrently modulating the immune response within the tumor microenvironment. Comprehensive in vitro and in vivo experiments demonstrated that Cu-VT NPs significantly inhibited tumor growth and reduced lung metastasis through cuproptosis induction. This dual-function composite material enhances therapeutic efficacy and minimizes side effects, showcasing its potential as a revolutionary treatment for BLCA. Our findings highlight the transformative potential of Cu-VT NPs in the context of BLCA treatment, establishing a new paradigm in the use of composite materials for the treatment of advanced cancer.
研究领域:
肿瘤学
·
分子生物学
·
纳米医学
·
免疫学
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Xiao Shuwei,Wang Pengchao,Zhao Jian,Ling Zhengyun,An Ziyan,Fu Zhouyang,Fu Weijun,Zhou Jin,Zhang Xu
The bladder patch constructed with the bladder acellular matrix (BAM) and adipose-derived stem cells (ASCs) was incubated with the omentum for bladder reconstruction in a rat model of bladder augmentation cystoplasty. A self-designed perfusion system and five different decellularization protocols were used to prepare the BAM. Finally, an optimal protocol (group C) was screened out by comparing the cell nucleus residue, collagen structure preservation and biologically active components retention of the prepared BAM. ASCs-seeded (BAM-ASCs group) and unseeded BAM (BAM group) were incubated with the omentum for 7 days to promote neovascularization and then perform bladder reconstruction. Hematoxylin and eosin and Masson’s trichrome staining indicated that the bladder patches in the BAM-ASCs group could better regenerate the bladder wall structure compared to the BAM group. Moreover, immunofluorescence analyses demonstrated that the ASCs could promote the regeneration of smooth muscle, neurons and blood vessels, and the physiological function (maximal bladder capacity, max pressure prior to voiding and bladder compliance) restoration in the BAM-ASCs group. The results demonstrated that the self-designed perfusion system could quickly and efficiently prepare the whole bladder scaffold and confirmed that the prepared BAM could be used as the scaffold material for functional bladder tissue engineering applications.
研究领域:
组织工程
·
干细胞研究
·
再生医学
·
泌尿学
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2024
·
IF 27.4
Kangkang Liu,Lining Wang,Jing Peng,Yuanji Lyu,Yiming Li,Dengyi Duan,Wenyi Zhang,Guojiang Wei,Taipeng Li,Yuanjie Niu,Yang Zhao
Intravesical Bacillus Calmette–Guérin (BCG) is a well-established strategy for managing high-risk nonmuscle-invasive bladder cancer (NMIBC); however, over half of patients still experience disease recurrence or progression. Although the combined intravesical instillation of various chemotherapeutic drugs is implemented in clinical trials to enhance the BCG therapy, the outcome is far from satisfying due to severe irritative effects and treatment intolerance at high doses. Therefore, it is adopted the “biotin–streptavidin strategy” to doxorubicin (DOX)-encapsulated nanoparticles within live BCG bacteria (DOX@BCG) to improve treatment outcomes. Adherence of BCG to the bladder epithelium helps precisely target DOX@BCG to the local tumor cells and simultaneously increases intratumoral transport of therapeutic drugs. DOX@BCG effectively inhibits cancer progression and prolongs the survival of rats/mice with orthotopic bladder cancer owing to synergism between BCG-immunotherapy, DOX-chemotherapy, and DOX-induced immunogenic tumor cell death; furthermore, it exhibits improved tolerance and biosafety, and establishes antitumor immunity in the tumor microenvironment. Therefore, the drug-loaded live BCG bacterial delivery system holds considerable potential for clinical translation in the intravesical treatment of bladder cancer.
研究领域:
肿瘤学
·
药理学
·
免疫治疗
·
纳米技术
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cancer Communications
·
2025
·
IF 24.9
Jie Zhang,Chen Zhang,Ruichen Zang,Weiwu Chen,Yining Guo,Haofei Jiang,Jing Le,Kunyu Wang,Haobo Fan,Xudong Wang,Sisi Mo,Peng Gao,Wenhao Guo,Xinrong Jiang,Fengbin Gao,Junming Jiang,Juyan Zheng,Yuxing Chen,Yicheng Chen,Yanlan Yu,Guoqing Ding
Background: Only a few bladder cancer patients benefit from anti-programmed cell death protein 1/programmed cell death ligand 1 immunotherapy. The cluster of differentiation 47 (CD47) plays an important role in tumor immune evasion. CD47 is a highly glycosylated protein, however, the mechanisms governing CD47 glycosylation and its potential role in immunosuppression are unclear. Therefore, this study aimed to evaluate the function of CD47 glycosylation in bladder cancer. Methods: Western blotting, immunohistochemistry, and flow cytometry were used to measure protein expression, protein-protein interactions, and phagocytosis in bladder cancer. A murine model was employed to investigate the impact of mannosidase alpha class 1B member 1 (MAN1B1) modification of CD47 on anti-phagocytosis in vivo. An ex vivo model, patient-derived tumor-like cell clusters, was used to examine the effect of targeting MAN1B1 on phagocytosis. Results: Our research identified that aberrant CD47 glycosylation was responsible for its immunosuppression. The glycosyltransferase MAN1B1 responsible for CD47 glycosylation was highly expressed in bladder cancer. Abnormal activation of extracellular signal-regulated kinase (ERK) was significantly associated with MAN1B1 stability by regulating the interaction between MAN1B1 and the E3 ubiquitin ligase HMG-CoA reductase degradation 1 (HRD1). Mechanistically, abnormally activated ERK stabilized MAN1B1, resulting in the glycosylation of CD47 and facilitating immune evasion by enhancing its interaction with signal-regulatory protein alpha (SIRP-α). In vitro and in vivo experiments demonstrated that MAN1B1 knockout weakened CD47-mediated anti-phagocytosis. MAN1B1 inhibitors promoted phagocytosis without causing anemia, offering a safe alternative to anti-CD47 therapy. Conclusions: This comprehensive analysis uncovered that ERK activation stabilizes MAN1B1 by regulating the interaction between MAN1B1 and HRD1, facilitates immune evasion via CD47 glycosylation, and presents new potential targets and strategies for cancer immunotherapy that do not cause anemia.
研究领域:
肿瘤学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Aging-US
·
2024
·
IF 3.9
Guang Wang,Pei Li,Si-Wei Su,Rui Xu,Zi-Ye Huang,Tong-Xin Yang,Jiong-Ming Li
Background: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition with painful bladder. At present, the pathogenesis of IC/BPS is still unknown. Quercetin (QCT) is a kind of natural flavonoid with wide sources and multiple biological activities. The purpose of this study was to explore the effects of QCT on mRNA expression and related regulatory signal pathways in IC model rats. Methods: LL-37 was used to induce the IC/BPS model rats. 20 mg/kg QCT was injected intraperitoneally into IC/BPS rats. ELISA, HE, Masson and TB staining were used to evaluate the level of inflammation and pathology. The concentration of QCT in rats was detected by HPLC. The mRNA sequencing was used to detect the differentially expressed (DE) mRNA in each group. The over-expression experiment of Lpl was carried out in IC/BPS model rats. Results: QCT treatment significantly decreased the level of MPO, IL-1β, IL-6 and TNF-α induced by LL-37 in rats, and alleviated bladder injury and mast cell degranulation. There were significant differences in mRNA sequencing data between groups, and the hub gene Lpl were screened by Cytohubba. The expression of Lpl was downregulated in IC/BPS rats. QCT intervention promoted Lpl expression. Overexpression of Lpl reduced the bladder injury induced by LL-37, increased GAG level and decreased the expression of MPO, IL-1β, IL-6 and TNF-α. Conclusion: In this study, we provided the DE mRNA in IC/BPS rats treated with QCT, the signaling pathways for DE enrichment, screened out the hub genes, and revealed that Lpl overexpression alleviated IC/BPS model rats.
研究领域:
药理学
·
分子生物学
·
生物信息学
·
泌尿学
✓ 已验证
DOI
PubMed
高影响因子
ACS Synthetic Biology
·
2019
·
IF 5.571
Jing Fan,Yuchen Liu,Lisa Liu,Yikun Huang,Xuemei Li,Weiren Huang
The treatment of bladder cancer has recently shown minimal progress. Gene therapy mediated by CRISPR provides a new option for bladder cancer treatment. In this study, we developed a versatile liposome system to deliver the CRISPR-Cas13a gene circuits into bladder cancer cells. After in vitro studies and intravesical perfusion studies in mice, this system showed five advantages: (1) CRISPR-Cas13a, a transcriptional targeting and cleavage tool for gene expression editing, did not affect the stability of the cell genome; (2) the prepared liposome systems were targeted to hVEGFR2, which is always highly expressed in bladder cancer cells; (3) the CRISPR-Cas13a sequence was driven by an artificial tumor specific promoter to achieve further targeting; (4) a near-infrared photosensitizer released using near-infrared light was introduced to control the delivery system; and (5) the plasmids were constructed with three crRNA tandem sequences to achieve multiple targeting and wider therapeutic results. This tumor cell targeting lipid delivery system with near-infrared laser-controlled ability provided a versatile strategy for CRISPR-Cas13a based gene therapy of bladder cancer.
研究领域:
癌症生物学
·
基因治疗
·
生物技术
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2024
·
IF 5.8
Shiya Zhuang,Xingwei Jin,Lian Cen,Yuan Shao
Intravesical instillation is an effective post-treatment for bladder cancer performed by delivering medications directly into the bladder to target the remaining cancer cells. The current study thus aimed to develop porous poly(L-lactide-co-ε-caprolactone) (PLCL) microspheres encapsulated with 10-hydroxycamptothecin (HCPT) via microfluidics to serve as a drug delivery system with persistent floating capacity and sustained HCPT-release property for intravesical instillation. A microfluidic device was designed to fabricate PLCL microspheres and encapsulate HCPT (HCPT-MS) within them; methanol and tridecane were introduced into an oil phase as a co-solvent and pore-forming agent, respectively, to regulate the floating ability of microspheres. The physicochemical properties of the resulting microspheres were characterized, and the floating behavior, release profile and anti-tumor effects of HCPT-MS were investigated. The obtained spherical HCPT-MS were 119.23 μm in size, monodisperse, and featured a porous concave surface and hollow structure. The encapsulation efficiency and drug loading of HCPT within HCPT-MS was around 67% and 4.9%, respectively. HCPT-MS exhibited impressive floating capabilities in water, PBS and artificial urine even in a simulated bladder dynamic environment. These microspheres remained afloat after being subjected to 90 repeated simulated urination processes. The sustained release of HCPT from these floating microspheres lasted for more than 10 days. The IC50 (half maximal inhibitory concentration) of HCPT-MS was calculated to be 52.14 μg mL−1. T24 cells (human bladder cancer cells) when cultured with HCPT-MS at such a concentration were severely inhibited, and the inhibition further enhanced with an increase in culture time. Hence, the feasibility of the current porous and floating HCPT-MS as a formulation for intravesical instillation to deliver medications into the bladder with sustained release and stability was thus substantiated.
研究领域:
药学
·
生物医学工程
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）